By Katrine Kirkeby Skeby
This thesis deals readers a finished creation to amyloid proteins and the computational tools used with them. Katrine Skeby significantly assesses and compares either the literature and the experiments played via different researchers, which additional elevates the standard and relevance of her personal paintings. Amyloid proteins are hugely advanced, and this study offers exceptional insights, particularly in regards to the foundation of cytotoxicity and to constructing applied sciences for early detection, revealing intimately the molecular mechanisms in the back of hIAPP habit. numerous stories in the thesis resolution tricky questions which advertise destiny study into the homes of amyloid proteins.
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Extra info for Computational Modelling of the Human Islet Amyloid Polypeptide
Each method has a timescale of which it can provide information ranging from vibrations of individual atoms on a sub-femtosecond timescale, to protein translation by the ribosome on a timescale of seconds . Most of the available techniques provide ensemble properties, and do not report on the dynamics of single proteins. MD simulation is a computational technique able to provide very high resolution in time and space which is unmatched by any experimental technique. It basically provides a three-dimensional movie of how the atoms in a system move relative to one another.
Proc Natl Acad Sci USA 102:6297–6302 135. Friedman R, Pellarin R, Caflisch A (2009) Amyloid aggregation on lipid bilayers and its impact on membrane permeability. J Mol Biol 387:407–415 136. Abedini A, Schmidt AM (2013) Mechanisms of islet amyloidosis toxicity in type 2 diabetes. FEBS Lett 587:1119–1127 137. Shim S, Gupta R, Ling YL, Strasfeld DB, Raleigh DP, Zanni MT (2009) Two-dimensional IR spectroscopy and isotope labeling deﬁnes the pathway of amyloid formation with residue-speciﬁc resolution.
This antibody was developed by injecting a rabbit with a molecular mimic of an Aβ oligomer. It was subsequently shown that the antibody did not react to Aβ monomers or mature ﬁbrils . It was also shown that the antibody, termed A11, speciﬁcally reacts with oligomers from other amyloidogenic peptides, including hIAPP . However, problems with using A11 to detect oligomers in tissue samples have been suggested, as the antibody has also been shown to react with several proteins with a natively globular fold .